WTX-330 / Werewolf Therap - LARVOL DELTA

Sequential IL-12 and IL-2 dosing enhanced antitumor activity with improved tolerability (GlobeNewswire) - "In mice bearing poorly immunogenic EMT6 tumors, a sequential regimen of mWTX-330 (IL-12) followed by WTX-124 (IL-2) was well tolerated and demonstrated superior tumor-killing ability compared to either drug alone. These data suggest that mWTX-330 (IL-12) primes the immune response, and WTX-124 (IL-2) subsequently amplifies it, leveraging their complementary mechanisms of action to create a potent and translatable therapeutic strategy."

Preclinical • Oncology

Sequential administration of WTX-124 and mWTX-330, IL-2 and IL-12 INDUKINE™ molecules, enhanced antitumor activity in mice bearing poorly immunogenic EMT6 tumors without systemic toxicity (SITC 2025) - "At the end of the study, ELISpot analysis demonstrated that mWTX-330 had primed tumor specific immune responses, which were further amplified by WTX-124.Conclusions We conclude that sequential administration of mWTX-330 and WTX-124 takes advantage of the complementary mechanisms of action of native IL-12 and IL-2, eliciting marked antitumor activity with improved tolerability compared to concurrent dosing regimens. We believe that this approach may be directly translatable to the clinical setting.Ethics Approval All mouse in vivo work was performed in accordance with current regulations and standards of the U.S. Department of Agriculture and the NIH at Charles River Laboratories with the approval of an Institutional Animal Care and Use Committee."

Preclinical • Oncology • CD8 • IFNG • IL12A • IL2 • ITGAE

WTX-330: (The Manila Times) - "Actively enrolling in a Phase 1b/2 clinical trial (WTX-330x2102) in locally advanced or metastatic solid tumors. An update on the clinical trial is expected to be released in the fourth quarter of 2025, with guidance on potential further development plans."

P1/2 data • Lymphoma • Solid Tumor

Werewolf Therapeutics to Present Posters at the Society for Immunotherapy of Cancer’s (SITC) 40th Annual Meeting (GlobeNewswire)

PK/PD data • Preclinical • Oncology

WTX-330: a systemically delivered, conditionally activated Interleukin-12 (IL-12) INDUKINE molecule being developed in advanced or metastatic solid tumors. (GlobeNewswire) - "Actively enrolling in a Phase 1b/2 clinical trial (WTX-330x2102) in locally advanced or metastatic solid tumors. Anticipate determination of dosing regimen by the end of 2025."

Trial status • Solid Tumor

Werewolf Therapeutics to Participate in Hanson Wade’s 6th Annual Cytokine-Based Drug Development Summit (GlobeNewswire) - "The presentation will highlight how data from patients treated with IL-2 and IL-12 INDUKINE molecules in first-in-human clinical trials have successfully validated Werewolf’s unique approach to engineering differentiated, tumor-activated immunotherapies."

Clinical data • Solid Tumor

A Phase 1b/2 Multisite Dose-finding and Expansion Study of WTX-330 in Adult Patients With Selected Advanced or Metastatic Solid Tumors or Lymphoma (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Werewolf Therapeutics, Inc.

IO biomarker • New P1/2 trial • Colorectal Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • IL12A • PD-L1

Werewolf Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "The cutaneous melanoma monotherapy dose-expansion arm of the Phase 1/1b clinical trial evaluating WTX-124 in a more homogeneous, less heavily pre-treated patient population is expected to be fully enrolled in the first half of 2025, and the cutaneous melanoma dose-expansion arm evaluating WTX-124 in combination with pembrolizumab is expected to be fully enrolled by the end of 2025. The Company expects to use the monotherapy and combination data to engage with regulators to discuss potential registrational pathways for WTX-124, including strategies for accelerated approval, in the second half of 2025. Anticipated presentation of interim data from monotherapy and combination expansion arms in the fourth quarter of 2025....On track to initiate a Phase 1/2 dose- and regimen-finding clinical trial by the end of the first quarter of 2025 to optimize the exposure of WTX-330 in the tumor microenvironment."

New P1/2 trial • P1 data • Trial status • Cutaneous Melanoma • Oncology • Solid Tumor

WTX-330x2101: WTX-330 in Patients With Advanced or Metastatic Solid Tumors or Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Werewolf Therapeutics, Inc. | Active, not recruiting ➔ Completed | N=75 ➔ 25

Enrollment change • Trial completion • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Werewolf Therapeutics Provides Business Update and Highlights 2025 Strategic Outlook (GlobeNewswire) - "WTX-330: Initiate a Phase 1/2 dose- and regimen-finding clinical trial in the first quarter of 2025 to optimize the delivery of WTX-330 to the tumor microenvironment."

New P1/2 trial • Solid Tumor

WTX-330x2101: WTX-330 in Patients with Advanced or Metastatic Solid Tumors or Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=75 | Active, not recruiting | Sponsor: Werewolf Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

The tumor-activated IL-12 prodrug WTX-330 expanded/activated tumor infiltrating lymphocytes and caused tumor regression in patients with refractory solid tumors: interim data from an ongoing Ph1 study (SITC 2024) - P1 | "At 0.024 mg/kg, a 76yo with diffuse in-transit metastatic melanoma who had progressed on adjuvant pembrolizumab achieved a RECIST PR (47% TL reduction). These include: Northwestern (IRB STU218585-CR0001), University of Pittsburgh (20230524), HonorHealth (WIRB, IRB-22-0043), Emory (WIRB, STUDY00004612), NEXT Oncology (Salus IRB, NXSAT21.151), Indiana University (IRB, 15531), Providence Cancer Institute (PSJH IRB, STUDY2022000507) and Roswell Park (STUDY00002189/P-3556923). All patients provided written informed consent prior to taking part in the study."

Clinical • IO biomarker • Tumor-infiltrating lymphocyte • Biliary Cancer • Cholangiocarcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL12A

Werewolf Therapeutics Reports Third Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "In the first half of 2025, Werewolf expects to provide an update on the WTX-124 clinical development program, including data from the monotherapy expansion arms that are evaluating WTX-124 in more homogenous, less heavily pre-treated patient populations to inform future development priorities....Research and development expenses were $12.5 million for the third quarter of 2024, compared to $10.8 million for the same period in 2023. The increase in research and development expenses was primarily due to the Company’s development efforts for WTX-124 and WTX-330, which continue to progress through their respective clinical trials, resulting in higher clinical trial costs and higher manufacturing costs to support those trials."

Commercial • P1 data • Oncology • Solid Tumor

Werewolf Therapeutics Presents…Clinical Data at the Society for Immunotherapy of Cancer’s (SITC) 39th Annual Meeting (GlobeNewswire) - P1 | N=75 | NCT05678998 | Sponsor: Werewolf Therapeutics, Inc. | "A Phase 1/2 dose- and regimen-finding clinical trial, designed to optimize WTX-330 exposure in the tumor microenvironment...is expected to begin enrolling in the first half of 2025; As of October 7, 2024, the study had enrolled twenty-five patients with diverse solid tumors, including microsatellite stable colorectal cancer (MSS CRC), cholangiocarcinoma, metastatic cutaneous melanoma, and non-small cell lung cancer....Evidence of IL-12 activity in the tumor microenvironment with four patients with MSS CRC showing evidence of tumor immune activation in on-treatment tumor biopsies; A 76 year old patient with diffuse in-transit metastatic melanoma who had progressed on adjuvant pembrolizumab achieved a Response Evaluation Criteria in Solid Tumors (RECIST) confirmed partial response."

New P1/2 trial • P1 data • Cholangiocarcinoma • Colorectal Cancer • Melanoma • Non Small Cell Lung Cancer

Werewolf Therapeutics to Present Posters at the Society for Immunotherapy of Cancer’s (SITC) 39th Annual Meeting (GlobeNewswire) - "Werewolf Therapeutics...announced that two posters will be presented at the upcoming Society for Immunotherapy of Cancer’s (SITC) 39th Annual Meeting, taking place November 6-10, 2024, in Houston, Texas."

P1 data • Preclinical • Solid Tumor

Werewolf Therapeutics Reports Second Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Upcoming Milestones...Dose escalation is ongoing for WTX-124 in combination with pembrolizumab, with updated data and opening of expansion arms anticipated in the second half of 2024; WTX-330: Werewolf anticipates sharing additional results from the checkpoint inhibitor-resistant or -naïve relapsed or refractory advanced tumor patient expansion arms in the fourth quarter of 2024."

P1 data • Hematological Malignancies • Lymphoma • Melanoma • Non-Hodgkin’s Lymphoma • Oncology • Skin Cancer • Solid Tumor

Werewolf Therapeutics Highlights Initial Safety and Efficacy Data from its Ongoing Phase 1 Clinical Trial Evaluating WTX-330 in Patients with Advanced or Metastatic Solid Tumors or Non-Hodgkin Lymphoma (GlobeNewswire) - P1 | N=75 | NCT05678998 | Sponsor: Werewolf Therapeutics, Inc. | "Compared to previous IL-12 therapeutic strategies (recombinant human IL-12 (rhIL-12) at 500 ng/kg (maximum tolerated dose)), at the 0.024 mg/kg dose, WTX-330 demonstrated an approximately 23-fold higher systemic drug concentration of IL-12 prodrug delivered to patients in the outpatient setting, with low free IL-12 levels across all dose levels (<1.6% of prodrug exposure)....One patient with metastatic melanoma who had previously progressed on adjuvant pembrolizumab was treated with 0.024 mg/kg WTX-330 administered intravenously once every two weeks (IV Q2W) and achieved an unconfirmed partial response by Response Evaluation Criteria in Solid Tumors (RECIST) after eight weeks with no evidence of disease on biopsy and marked decreased uptake on positron emission tomography (PET) imaging....The Company has opened two expansion arms evaluating 0.024 mg/kg of WTX-330."

P1 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Melanoma • Non-Hodgkin’s Lymphoma • Oncology • Skin Cancer • Solid Tumor

Werewolf Therapeutics Reports First Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "At the American Society for Clinical Oncology (ASCO) Annual Meeting, the Company will present additional interim data from the monotherapy dose-escalation arm and preliminary dose-escalation data from the combination arm of its ongoing Phase 1/1b clinical trial of WTX-124....Werewolf remains on track to select a recommended dose for expansion and initiate monotherapy dose expansion arms in the first half of 2024....In the second quarter of 2024, Werewolf plans to present interim first-in-human data from Study WTX-330x2101, its Phase 1, multi-center, open-label clinical trial evaluating WTX-330 as a monotherapy in patients with immunotherapy insensitive or resistant advanced or metastatic solid tumors or non-Hodgkin lymphoma."

P1 data • Trial status • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

WTX-330 in Patients With Advanced or Metastatic Solid Tumors or Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=75 | Recruiting | Sponsor: Werewolf Therapeutics, Inc. | Trial primary completion date: Nov 2023 ➔ Dec 2024

Metastases • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Werewolf Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Update (GlobeNewswire) - "In the first half of this year, we plan to present additional clinical data from our Phase 1/1b clinical trial of WTX-124, including updated monotherapy data and initial combination data, which we anticipate will build on the promising signals of antitumor activity and improved therapeutic index that we observed in the data presented at SITC last year. In addition, we plan to share data further demonstrating the performance of our platform in our preclinical programs at AACR. We also plan to share initial clinical data from WTX-330, our second clinical candidate, in the second quarter of 2024."

P1 data • Preclinical • Non-Hodgkin’s Lymphoma • Solid Tumor

Werewolf Therapeutics Provides Business Update and Highlights 2024 Strategic Outlook (GlobeNewswire) - "WTX-330: In 2024, Werewolf plans to report initial data from the Phase 1 clinical trial in the second quarter of 2024."

P1 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Werewolf Therapeutics Reports Third Quarter 2023 Financial Results and Provides Business Update (Yahoo Finance) - "Research and development expenses: Research and development expenses were $10.8 million for the third quarter of 2023, compared to $13.1 million for the same period in 2022. The decrease in research and development expenses was primarily due to a decrease in contract manufacturing costs associated with WTX-124 and WTX-330. The decline in contract manufacturing costs was partially offset by an increase in clinical trial costs for WTX-124 and WTX-330."

Commercial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Spatial analysis of tumor infiltrating lymphocyte populations in syngeneic mouse tumor models after treatment with IL-12 (mWTX-330) and IL-2 (WTX-124) INDUKINETM molecules (SITC 2023) - "This phenomenon was further amplified by combination treatment with blockers of the PD-1 pathway, highlighting the potential for INDUKINETM treatments to amplify the effects of checkpoint inhibitors. Conclusions Treatment of murine tumor bearing mice with either mWTX-330 or WTX-124 resulted in significant remodeling of immune cell populations found within the tumor tissue, simultaneously increasing immune cell infiltration, and generating a potent activation of effector cells."

IO biomarker • Preclinical • Tumor-infiltrating lymphocyte • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • GZMB • IL12A • IL2

Werewolf Therapeutics to Present Clinical and Preclinical Data at the Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting (GlobeNewswire) - "Additional posters with preclinical data supporting the PREDATOR platform and INDUKINE product candidates will also be presented at the meeting....Tumor growth over time was measured in mice bearing syngeneic tumors treated with either mWTX-330 (a chimeric IL-12 containing INDUKINE molecule) or WTX-124 (a human IL-2 containing INDUKINE molecule) using various techniques, including high-plex immunofluorescence, resulting in significant remodeling of immune cell populations found within the tumor tissue and simultaneously increased immune cell infiltration generating a potent activation of effector cells....Systemic administration of WTX-124 resulted in robust antitumor immunity and preferentially activated tumor-infiltrating immune cells as compared to a non-alpha IL-2 version of the INDUKINE demonstrating that the full activity of IL-2 contained in WTX-124 is required to activate potent antitumor responses."

Preclinical • Oncology

Werewolf Therapeutics Announces Upcoming Presentations at the Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting (GlobeNewswire) - "Six abstracts, spanning Werewolf’s PREDATOR™ platform and INDUKINE™ pipeline, accepted for poster presentations at SITC annual meeting; Company to present interim first-in-human clinical data from initial monotherapy dose-escalation cohorts in ongoing Phase 1/1b study of WTX-124."

P1 data • Preclinical • Oncology • Solid Tumor